Calculated Activation Barriers Research Articles

The Importance of Reaction Energy in Predicting Chemical Reaction Barriers with Machine Learning Models.

Improving our fundamental understanding of complex heterocatalytic processes increasingly relies on electronic structure simulations and microkinetic models based on calculated energy differences. In particular, calculation of activation barriers, usually achieved through compute-intensive saddle point search routines, remains a serious bottleneck in understanding trends in catalytic activity for highly branched reaction networks. Although the well-known Brønsted-Evans-Polyani (BEP) scaling - a one-feature linear regression model - has been widely applied in such microkinetic models, they still rely on calculated reaction energies and may not generalize beyond a single facet on a single class of materials, e. g., a terrace sites on transition metals. For highly branched and energetically shallow reaction networks, such as electrochemical CO2 reduction or wastewater remediation, calculating even reaction energies on many surfaces can become computationally intractable due to the combinatorial explosion of states that must be considered. Here, we investigate the feasibility of activation barrier prediction without knowledge of the reaction energy using linear and nonlinear machine learning (ML) models trained on a new database of over 500 dehydrogenation activation barriers. We also find that inclusion of the reaction energy significantly improves both classes of ML models, but complex nonlinear models can achieve performance similar to the simplest BEP scaling when predicting activation barriers on new systems. Additionally, inclusion of the reaction energy significantly improves generalizability to new systems beyond the training set. Our results suggest that the reaction energy is a critical feature to consider when building models to predict activation barriers, indicating that efforts to reliably predict reaction energies through, e. g., the Open Catalyst Project and others, will be an important route to effective model development for more complex systems.

Double-proton transfer triggering mechanism of nitromethane caused by intermolecular hydrogen bonding at low temperature

The initial triggering mechanism of nitromethane is investigated by first-principles molecular dynamics simulations and temperature-dependent Raman spectroscopy experiment. The Raman spectra at different temperature are obtained by Car-Parrinello molecular dynamics simulation to explore the activated vibration modes caused by low-temperature heat. The temperature-dependent Raman spectra experiment is constructed to compare with the theoretical data. Each possible initial reaction path caused by the activated vibration mode is analyzed to reveal the triggering mechanism of the initial chemical bond breaking for nitromethane. The results show that the intermolecular double-proton transfer is the first reaction step which is triggered by the intermolecular hydrogen bond reinforced with the active C–H stretching vibration (near 3000 cm−1), which is not reported before. The scanning energy barrier related to the increase of C–H bond lengths is about 60 kcal/mol, which is consistent with the calculated activation barrier (59.8 kcal/mol) of intermolecular proton transfer reaction. This proves the reliability of our conclusions. The results provide a new interpretation for the long-debated initial decomposition mechanism of nitromethane.

Theoretical study on NO oxidation using single metal atom catalysis embedded graphene with N4 vacancy

This work investigates the potential NO oxidation schemes using a graphene with N4 vacancy (GrN4) monolayer doped with transition metals (TM = Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, and Zn) for single-atom catalysis (SAC). The GrN4 monolayer is proven capable of greatly suppressing the clustering tendency of TM atoms due to its strong binding ability. Moreover, the Ti-GrN4 systems exhibit considerable affinity towards both NO and O2, meeting a fundamental criterion for kick-starting the catalytic cycle. Three dissimilar mechanisms: Eley-Rideal (ER), Langmuir-Hinshelwood (LH), and trimolecular Eley-Rideal (TER) mechanisms were examined for the NO oxidation in Ti-GrN4 SAC. The calculated activation barriers indicate that the LH pathway is the preferred mechanism, in which the NO + O2 reaction can form the OONO intermediate, then generate and release NO2 molecules. Therefore, Ti-supported GrN4 has the potential to be a strong single-atom catalyst for NO oxidation at low temperatures.

Solvent and Substituent Size Influence on the Cyclochiral Rigidity of Aminomethylene Derivatives of Resorcin[4]arene.

Resorcin[4]arenes (R[4]A) are a group of macrocyclic compounds whose peculiar feature is the presence of eight hydroxyl groups in their structure. The directional formation of intramolecular hydrogen bonds with their participation leads to the formation of a cyclochiral racemic mixture of these compounds. Their stability strongly depends on the substituent and especially the environment in which they are located. The paper discusses the cyclochiral nature of aminomethylene derivatives of R[4]A (AMD-R[4]A). Their cyclochiral rigidity in non-polar solvents has been shown. The influence of the size of the alkyl groups in the amino substituents of AMD-R[4]A on their cyclochiral nature was noted. To calculate the reaction paths for their racemization, the nudged elastic band (NEB) method was employed using the semi-empirical DFT (GFN1-xTB) approach. The calculated activation barrier energies for their racemization in chloroform, obtained through various semi-empirical quantum chemical methods (SE), Hartree-Fock (HF), and density functionals theory (DFT), show good correlation with experimental observations. Among the tested methods, the B38LYP-D4 method is highly recommended due to its fast computational speed and accuracy, which is comparable to the time-consuming double-hybrid DH-revDSD-PBEP86 approach.

Discovering a Single‐Atom Catalyst for CO2 Electroreduction to C1 Hydrocarbons: Thermodynamics and Kinetics on Aluminum‐Doped Copper

AbstractThe electrochemical reduction of carbon dioxide (CO2) to hydrocarbons is a potential option to achieve carbon neutrality. Although copper (Cu) shows the highest activity for the CO2 reduction reaction (CO2RR) to hydrocarbons among metals, high reaction overpotentials and significant H2 production limit its use. We investigate single‐atom alloys (SAAs) of ten metals (Ag, Au, Fe, Ir, Ni, Pd, Pt, Rh, Ru, Al) on Cu(111), which is the most‐favored facet on Cu for methane production, using density functional theory. We examined the dopants’ ability to lower the free energy of the elementary reaction, *CO to *CHO, which is the potential‐determining step (PDS). Out of the SAAs studied, only Al‐doped Cu demonstrated a lowering of the PDS free energy. Additionally, weaker adsorption energies of *CO and *H on Al−Cu(111) suggest a preference for C1 hydrocarbons and inhibition of H2 evolution. Finally, activation barrier calculations for the PDS on Al−Cu(111) involving an explicitly hydrated proton indicated better intrinsic activity for C1 hydrocarbons compared to pure Cu(111). We also confirmed the stability of Al−Cu SAA compared to small Al clusters. Through a comprehensive study of both thermodynamics and kinetics, our study presents Al−Cu SAA as a promising catalyst for CO2 electroreduction to C1 hydrocarbons.

First principles investigation of cobalt-phthalocyanine active site tuning via atomic linker immobilization for CO2 electroreduction

We investigate the CO2 electroreduction reaction (CO2ERR) using first principles calculations, for the active site tuning of cobalt phthalocyanine (CoPc) via distinct atomic linker species which immobilize CoPc on a carbon nanotube (CNT) substrate. Eight different linker species are studied, along with the effect of linker hydrogenation. Superior reaction performance is predicted for the NH, S and PH linkers, which show activated CO2 adsorption. This results from spin polarization causing unoccupied dz2 spin-down states of the cobalt active site at, or above, the Fermi level. Using an ‘on-catalyst’ reaction scheme, calculated activation barriers for COOH formation and CO desorption are lower for the CoPc-PH-CNT system compared to the CoPc-NH-CNT system and CoPc remains attached to PH-CNT throughout the reaction. We thus expect the PH linker system to have similar or better CO2ERR performance compared to the NH and S linker systems but at a slightly higher electrode potential.

Excited-State Intramolecular Proton Transfer in Salicylidene-α-Hydroxy Carboxylate Derivatives: Direct Detection of the Triplet Excited State of the cis-Keto Tautomer.

Excited-state intramolecular hydrogen transfer on the triplet surface of salicylideneaniline derivatives has received much less attention than the corresponding ultrafast process on the singlet surface. To enhance the understanding of this triplet reactivity, the photochemical properties of a series of salicylidene-α-hydroxy acid salts with different substituents on the phenol moiety (1-3) were characterized. UV/vis absorption and phosphorescence measurements in ethanol revealed that 1-3 exist as both enol and keto tautomers, with the enol form being predominant. Irradiation of 1 at 310 nm in ethanol glass (77 K) yielded an absorption band with a λmax at ∼405 nm, which was assigned to the trans-keto tautomer (trans-1K). In contrast, laser flash photolysis of 1-3 in methanol or acetonitrile resulted in a transient absorption with λmax at 440-460 nm. This transient, which decayed on the microsecond timescale and was significantly shorter lived in methanol than in acetonitrile, was assigned to the triplet excited state (T1) of the cis-keto tautomer (cis-1K-3K) and residual absorption of trans-1K-3K by comparison with TD-DFT calculations. The assignment of the T1 of cis-1K was further supported by quenching studies with anthracene and 2,5-dimethyl-2,4-hexadiene. Laser flash photolysis of 1 in the temperature range of 173-293 K gave an activation barrier of 6.7 kcal/mol for the decay of the T1 of cis-1K. In contrast, the calculated activation barrier for cis-1K to undergo a 1,5-H atom shift to reform 1 was smaller, indicating that intersystem crossing of the T1 of cis-1K is the rate-determining step in the regeneration of 1.

Alternating Metal‐Ligand Coordination Improves Electrocatalytic CO2 Reduction by a Mononuclear Ru Catalyst**

AbstractMolecular electrocatalysts for CO2‐to‐CO conversion often operate at large overpotentials, due to the large barrier for C−O bond cleavage. Illustrated with ruthenium polypyridyl catalysts, we herein propose a mechanistic route that involves one metal center that acts as both Lewis base and Lewis acid at different stages of the catalytic cycle, by density functional theory in corroboration with experimental FTIR. The nucleophilic character of the Ru center manifests itself in the initial attack on CO2 to form [Ru‐CO2]0, while its electrophilic character allows for the formation of a 5‐membered metallacyclic intermediate, [Ru‐CO2CO2]0,c, by addition of a second CO2 molecule and intramolecular cyclization. The calculated activation barrier for C−O bond cleavage via the metallacycle is decreased by 34.9 kcal mol−1 as compared to the non‐cyclic adduct in the two electron reduced state of complex 1. Such metallacyclic intermediates in electrocatalytic CO2 reduction offer a new design feature that can be implemented consciously in future catalyst designs.

Alternating Metal-Ligand Coordination Improves Electrocatalytic CO2 Reduction by a Mononuclear Ru Catalyst.

Molecular electrocatalysts for CO2 -to-CO conversion often operate at large overpotentials, due to the large barrier for C-O bond cleavage. Illustrated with ruthenium polypyridyl catalysts, we herein propose a mechanistic route that involves one metal center that acts as both Lewis base and Lewis acid at different stages of the catalytic cycle, by density functional theory in corroboration with experimental FTIR. The nucleophilic character of the Ru center manifests itself in the initial attack on CO2 to form [Ru-CO2 ]0 , while its electrophilic character allows for the formation of a 5-membered metallacyclic intermediate, [Ru-CO2 CO2 ]0,c , by addition of a second CO2 molecule and intramolecular cyclization. The calculated activation barrier for C-O bond cleavage via the metallacycle is decreased by 34.9 kcal mol-1 as compared to the non-cyclic adduct in the two electron reduced state of complex 1. Such metallacyclic intermediates in electrocatalytic CO2 reduction offer a new design feature that can be implemented consciously in future catalyst designs.

Theoretical prediction of the catalytic efficiency of non-metalated pincer-like phosphorus compounds for the hydrogenation of carbon-monoxide with ammonia-borane

The catalytic hydrogenation of carbon monoxide (CO) with ammonia-borane (NH3BH3) using a series of phosphorus compounds (1) has been explored computationally. The formation of an active phosphorus compound (1-H) via the subsequent transfer of protic and hydridic hydrogens from NH3BH3 to 1 is the initiation step. The newly formed catalyst (1-H) further carries out the conversion of CO to formaldehyde (HCHO) to methanol (MeOH). The impact of ONO-ligand substitution and ONO-framework modification on the catalytic efficiency is also studied. The catalytic efficiencies of the phosphorus compounds have been compared based on the calculated activation barriers of rate-determining step (RDS).

First-principles study of mercaptoundecanoic acid molecule adsorption and gas molecule penetration onto silver surface: an insight for corrosion protection.

Recently, 11-mercaptoundecanoic acid (MUA) molecule has attracted attention as a promising passivation agent of Ag nanowire (NW) network electrode for corrosion inhibition, but the underneath mechanism has not been elaborated. In this work, we investigate adsorption of MUA molecule on Ag(1 0 0) and Ag(1 1 1) surface, adsorption of air gas molecules of H2O, H2S and O2 on MUA molecular end surface, and their penetrations into the Ag surface using the first-principles calculations. Our calculations reveal that the MUA molecule is strongly bound to the Ag surface with the binding energies ranging from -0.47 to -2.06 eV and the Ag-S bond lengths of 2.68-2.97 Å by Lewis acid-base reaction. Furthermore, we find attractive interactions between the gas molecules and the MUA@Ag complexes upon their adsorptions and calculate activation barriers for their migrations from the outermost end of the complexes to the top of Ag surface. It is found that the penetrations of H2O and H2S are more difficult than the O2 penetration due to their higher activation barriers, while the O2 penetration is still difficult, confirming the corrosion protection of Ag NW network by adsorbing the uniform monolayer of MUA. With these findings, this work can contribute to finding a better passivation agent in the strategy of corrosion protection of Ag NW network electrode.

Mechanism of ammonia synthesis on Fe3Mo3N.

Ammonia (NH3) synthesis is an essential yet energy-demanding industrial process. Hence, there is a need to develop NH3 synthesis catalysts that are highly active under milder conditions. Metal nitrides are promising candidates, with the η-carbide Co3Mo3N having been found to be more active than the industrial Fe-based catalyst. The isostructural Fe3Mo3N catalyst has also been identified as highly active for NH3 synthesis. In the present work, we investigate the catalytic ammonia synthesis mechanisms in Fe3Mo3N, which we compare and contrast with the previously studied Co3Mo3N. We apply plane-wave density functional theory (DFT) to investigate surface N vacancy formation in Fe3Mo3N, and two distinct ammonia synthesis mechanisms. The calculations reveal that whilst N vacancy formation on Fe3Mo3N is more thermodynamically demanding than for Co3Mo3N, the formation energies are comparable, suggesting that surface lattice N vacancies in Fe3Mo3N could facilitate NH3 synthesis. N2 activation was found to be enhanced on Fe3Mo3N compared to Co3Mo3N, for adsorption both at and adjacent to the vacancy. The calculated activation barriers suggest that, as for Co3Mo3N, the associative Mars van Krevelen mechanism affords a much less energy-demanding pathway for ammonia synthesis, especially for initial hydrogenation processes.

Computational Predictions of the Hydrolysis of 2,4,6-Trinitrotoluene (TNT) and 2,4-Dinitroanisole (DNAN).

Hydrolysis is a common transformation reaction that can affect the environmental fate of many organic compounds. In this study, three proposed mechanisms of alkaline hydrolysis of 2,4,6-trinitrotoluene (TNT) and 2,4-dinitroaniline (DNAN) were investigated with plane-wave density functional theory (DFT) combined with ab initio and classical molecular dynamics (AIMD/MM) free energy simulations, Gaussian basis set DFT calculations, and correlated molecular orbital theory calculations. Most of the computations in this study were carried out using the Arrows web-based tools. For each mechanism, Meisenheimer complex formation, nucleophilic aromatic substitution, and proton abstraction reaction energies and activation barriers were calculated for the reaction at each relevant site. For TNT, it was found that the most kinetically favorable first hydrolysis steps involve Meisenheimer complex formation by attachment of OH- at the C1 and C3 arene carbons and proton abstraction from the methyl group. The nucleophilic aromatic substitution reactions at the C2 and C4 arene carbons were found to be thermodynamically favorable. However, the calculated activation barriers were slightly lower than in previous studies, but still found to be ΔG‡ ≈ 18 kcal/mol using PBE0 AIMD/MM free energy simulations, suggesting that the reactions are not kinetically significant. For DNAN, the barriers of nucleophilic aromatic substitution were even greater (ΔG‡ > 29 kcal/mol PBE0 AIMD/MM). The most favorable hydrolysis reaction for DNAN was found to be a two-step process in which the hydroxyl first attacks the C1 carbon to form a Meisenheimer complex at the C1 arene carbon C1-(OCH3)OH-, and subsequently, the methoxy anion (-OCH3) at the C1 arene carbon dissociates and the proton shuttles from the C1-OH to the dissociated methoxy group, resulting in methanol and an aryloxy anion.

Tetranuclear Copper Complexes with Bulky Aminoalcohol Ligands as Catalysts for Oxidative Phenoxazinone Synthase-like Coupling of Aminophenol: A Combined Experimental and Theoretical Study

The new copper(II) complexes [Cu4(pa)4(Bae)4]·H2O (1) and [Cu4(eba)4(Buae)4]·H2O (2) (Hpa = propionic acid, HBae = 2-benzylaminoethanol, Heba = 2-ethylbutyric acid and HBuae = 2-butylaminoethanol) were synthesizsed by the interaction of a copper salt with a methanol solution of the respective ligands. The single-crystal X-ray diffraction analysis reveals that both compounds have a {Cu4(μ3-O)4} cubane-like core. Both compounds show pronounced phenoxazinone synthase-like activity towards the aerobic oxidation of o-aminophenol to phenoxazinone chromophore, with the maximum initial rates W0 up to 3.5 × 10−7 M s−1, and exhibit complex non-linear W0 vs. [catalyst]0 dependences. DFT//CCSD theoretical calculations (B3LYP/ma-def2-TZVP//DLPNO-CCSD(T)/ma-def2-TZVPP) were employed to investigate the most challenging steps of catalyst-free and copper-catalysed o-aminophenol oxidation (formation of o-aminophenoxyl radical). QTAIM analysis was used to study the key intermediates and weak interactions. Geometries and energies of intermediates and transition states were benchmarked against a series of popular DFT functionals. The results of the calculations demonstrate that a CuII–OO• copper-superoxo model catalyst decreases the calculated activation barrier from 28.7 to 19.9 kcal mol−1 for the catalyst-free and copper-catalysed abstraction of the H atom from the hydroxyl group of o-aminophenol, respectively. Finally, both complexes 1 and 2 were studied as catalysts in the amidation of cyclohexane with benzamide to give N-cyclohexyl benzamide and N-methyl benzamide employing di-tert-butyl peroxide (DTBP) as the oxidant, with a conversion of 16%, and in the oxidation of cyclohexane to cyclohexanol with aq. H2O2, with a conversion of 12%.

Multiscale Study of Functional Acetylation of Cellulose Nanomaterials by Design: Ab Initio Mechanisms and Chemical Reaction Microkinetics

Cellulose nanomaterials, namely cellulose nanocrystals (CNCs) and cellulose nanofibrils (CNFs), present a class of multipurpose, renewable, biodegradable, and nontoxic materials, paving the way into the future of biobased materials. The abundance of hydroxyl groups on the surface allows modification of the materials properties according to application; however, to fully exploit their potential, better compatibility on the molecular level with the hydrophobic matrixes has to be explored beyond lab scale. One of the main missing pieces in functionalization of nanomaterials is a lack of studies focusing on mechanisms and kinetics, which are prerequisite for further optimization of conditions leading to optimal process in terms of both sustainable processing and optimal performance. In this study, the “by design” based approach to tailor biomaterial properties has been simulated multiscale-wise, thus providing a greatly needed input for commercialization. The microkinetic parameters of the elementary reaction steps for acetylation of two distinct types of cellulose nanomaterials were determined and refined by regression analysis. Ab initio part utilizes the density functional theory (DFT) for cellotriose as a model, which suggested that products were obtained through a mechanism consisting of active intermediate formation/subsequent competing one- or two-step (through binding/decomposition of complex) reactions. Quantum chemical simulations were used to pinpoint the most probable sequence through calculated activation barriers that served as a foundation for the development of a thorough regression analysis on experimental data sets. The yield of reaction, through formed acetyl groups was determined through Fourier transform infrared spectroscopy, leading to acquisition of critical elementary characteristics.

Unravelling the Potential of Ylides in Stabilizing Low-Valent Group 13 Compounds: Theoretical Predictions of Stable, Five-Membered Group 13 (Aluminum and Gallium) Carbenoids Capable of Small-Molecule Activation.

Computational investigations provide evidence toward the remarkable ability of strongly electron-donating ylidic functionalities in stabilizing singlet group 13 carbenoids with promising ligand properties. All of the proposed carbenoids are found to be considerably nucleophilic and possess significant singlet-triplet energy separation values. The calculated activation barriers and reaction free energies obtained for the cleavage of different enthalpically strong bonds by these carbenoids are found to be either comparable to or lower than those of the experimentally evaluated aluminum and gallium carbenoids, thereby indicating their potential in small-molecule activation.

Screening of transition metal doped two-dimensional C2N (TM-C2N) as high-performance catalyst for the non-oxidative propane dehydrogenation

Since last decade, single atom catalysts have massive development in the field of propane dehydrogenation (PDH). In this study, both the catalytic activity and reaction mechanism of 3d, 4d, and 5d transition metal atom anchored on C2N (TM-C2N) for non-oxidative PDH are studied in detail using the density functional theory methods. Firstly, six stable catalysts (Cr-, Mn-, Fe-, Co-, Cu-, and Ag-C2N) are screened out by calculating the difference between the formation energy of the single atom and the cohesive energy of the corresponding bulk metal. Combining the results of adsorption energy and density of states, it is demonstrated that propane and propylene can be stably adsorbed on all screened TM-C2N. The calculated activation barrier and reaction energy of elementary reactions involved in PDH indicate that the initial C−H bond breaking step is determined as the rate-determining step on almost all the screened TM-C2N catalysts. Among all studied TM-C2N, the Fe-C2N possesses excellent catalytic activity even better than other promising catalysts. In addition, the d-band center values of transition metal atoms in screened TM-C2N show a stronger liner relationship with the interaction energy, suggesting that the d-band center may be served as a priority descriptor for the interaction energy between reaction species and catalyst surface rather than for the adsorption energy of reaction species.

Computational Analysis of Histone Deacetylase 10 Mechanism by the ONIOM Method: A Complementary Approach to X-ray and Kinetics Studies.

Histone deacetylase 10 (HDAC 10) catalyzes deacetylation of N8-acetylspermidine into spermidine in the cytosolic region of eukaryotic cells. Inhibition of HDAC 10 has clinical importance in certain types of cancers. Recently, X-ray crystal structures corresponding to the substrate-bound, tetrahedral intermediate-bound, and product-bound enzymes have been resolved using variant forms of humanized HDAC 10. Based on these structures, it was proposed that Y307 residue polarizes the carbonyl of the acetyl group in N8-acetylspermidine together with a zinc atom, which is coordinated by D174, H176, D267, and an H2O molecule. The H2O molecule undergoes nucleophilic addition to the carbonyl carbon of N8-acetylspermidine to form the tetrahedral intermediate. During this process, it is suggested that H136 acts as a general base to deprotonate the H2O molecule. It is further proposed that the protonation of the amide N atom of the tetrahedral intermediate by H137 causes the deacetylation forming the final products, spermidine and acetate ion. In this study, computational models based on the ONIOM method were employed to study the proposed mechanism for the two steps of the deacetylation process based on the crystal structure of the substrate-bound enzyme. The energy profiles of each step as well as the roles of the active site residues were investigated for the catalysis. The calculated activation barrier is in good agreement with the reported kcat value.

Unexpected role of electronic coupling between host redox centers in transport kinetics of lithium ions in olivine phosphate materials.

The discrepancy between the trend in the diffusion coefficient of a lithium ion (DLi+) and that in the activation energy of ion hopping signals hidden factors determining ion transport kinetics in layered olivine phosphate materials (LiMPO4). Combining density functional theory (DFT) calculations and the Landau–Zener electron transfer theory, we unravel this hidden factor to be the electronic coupling between redox centers of the host materials. The ion transport process in LiMPO4 is newly described as an ion-coupled electron transfer (ET) reaction, where the electronic coupling effect on DLi+ is considered by incorporating the electronic transmission coefficient into the rate constant of the transfer reaction. The new model and DFT calculation results rationalize experimental values of DLi+ for various LiMPO4 (M = Fe, Mn, Co, Ni) materials, which cannot be understood solely by the calculated activation barrier of ion hopping. Interestingly, the electronic coupling between host redox centers is found to play an essential role. Particularly, the sluggish ion mobility in LiFePO4 is due to a very weak electronic coupling. The obtained insights imply that one can improve the rate performance of intercalation materials for metal-ion batteries through modifying the electronic coupling between redox centers of host materials.

Nonenzymatic Deamidation Mechanism on a Glutamine Residue with a C-Terminal Adjacent Glycine Residue: A Computational Mechanistic Study

The deamidation of glutamine (Gln) residues, which occurs non-enzymatically under physiological conditions, triggers protein denaturation and aggregation. Gln residues are deamidated via the cyclic glutarimide intermediates to l-α-, d-α-, l-β-, and d-β-glutamate residues. The production of these biologically uncommon amino acid residues is implicated in the pathogenesis of autoimmune diseases. The reaction rate of Gln deamidation is influenced by the C-terminal adjacent (N +1) residue and is highest in the Gln-glycine (Gly) sequence. Here, we investigated the effect of the (N + 1) Gly on the mechanism of Gln deamidation and the activation barrier using quantum chemical calculations. Energy-minima and transition-state geometries were optimized by the B3LYP density functional theory, and MP2 calculations were used to obtain the single-point energy. The calculated activation barrier (85.4 kJ mol−1) was sufficiently low for the reactions occurring under physiological conditions. Furthermore, the hydrogen bond formation between the catalytic ion and the main chain of Gly on the C-terminal side was suggested to accelerate Gln deamidation by stabilizing the transition state.